The goal of this project has been to use the SIV infected macaque model for the development of surgical, virological and immunological methods and to demonstrate the feasibility and efficacy of thymic transplantation for immune reconstitution that could be applied to human AIDS patients. A major change has been the virus more recently used - from SIV/MAN or SIV/Fgb which did not affect the thymus uniformly - to the molecular cloned SHIV(KB9). This virus (obtained from Dr. J. Sodroski) causes very rapid CD4 T cell decreases (<100/cumm), associated with thymus destruction within 4-6 weeks, with animals still surviving for 6 or more months. Another improvement has been to develop laparoscopic methods to biopsy the thymic tissues implanted in the omentum. Improved immunological methods (in collaboration with Dr. Z. Chen) have included the potential of following viral effects and thymic-related T cell reconstitution by two assays (a) T cell receptor ( CDR3 profiles i n CD4+ T cells (a manuscript -in press- reports the virus-induced clonal dominance involvement in the disruption of the T cell repertoire); (b) thymic output lymphocyte enumerations, which should help to denote the incapacity of the immune system to be improved by antiretroviral therapy alone, and to demonstrate the efficacy of thymic transplantation to reconstitute new T cell clones. Another finding, which could prove important regarding use of pigtail monkeys for vaccine studies, has been noting that the CD2 monoclonal antibody, used to detect CD8+ cells, measures only about half of the CD3+ T cells, using a CD3 monoclonal antibody (clone SP34). The CD2+CD8+ cells, identified as being activated NK cells, are most prominent in pigtail monkeys (compared to rhesus macaques or sooty mangabeys), and may explain the usually greater susceptibility of pigtail macaques to several SIV strains (MS submitted). FUNDING NIH / NIAID $126,890 5/01/96 - 4/30/01 PUBLICATIONS Zhou, D, Kou, Z, Ibegbu, C, Shen, Y, Lee-Parritz, D, Sehgal, P, McClure, H.M., Nahmias, A.J. and Chen, Z.W. The disruption of macaque CD4+ T cell repertoires during the primary simian immunodeficiency virus infection. J. Med. Prim. (In press). P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center
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